[go: up one dir, main page]

WO1993020956A1 - Procede de test des aerosols - Google Patents

Procede de test des aerosols Download PDF

Info

Publication number
WO1993020956A1
WO1993020956A1 PCT/US1993/003620 US9303620W WO9320956A1 WO 1993020956 A1 WO1993020956 A1 WO 1993020956A1 US 9303620 W US9303620 W US 9303620W WO 9320956 A1 WO9320956 A1 WO 9320956A1
Authority
WO
WIPO (PCT)
Prior art keywords
aerosol
heat loss
mass
mdi
measuring
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1993/003620
Other languages
English (en)
Inventor
Rix Earl Evans
Alec Parker Flowers, Jr.
David Erwin Hockaday
David Wayne Loar
James Kenneth Proctor
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GlaxoSmithKline LLC
Original Assignee
Glaxo Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glaxo Inc filed Critical Glaxo Inc
Priority to JP51864193A priority Critical patent/JP3249121B2/ja
Priority to EP93912291A priority patent/EP0637270B1/fr
Priority to DE69332201T priority patent/DE69332201T2/de
Priority to FI944910A priority patent/FI944910L/fi
Priority to AT93912291T priority patent/ATE222353T1/de
Priority to AU42894/93A priority patent/AU668183B2/en
Publication of WO1993020956A1 publication Critical patent/WO1993020956A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0065—Inhalators with dosage or measuring devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F1/00—Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow
    • G01F1/68—Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by using thermal effects
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F25/00—Testing or calibration of apparatus for measuring volume, volume flow or liquid level or for metering by volume
    • G01F25/0092—Testing or calibration of apparatus for measuring volume, volume flow or liquid level or for metering by volume for metering by volume

Definitions

  • This invention relates to a method of measuring the mass of an aerosol for ⁇ mulation delivered from a container after activation of a metered dose valve.
  • Aerosol drug formulations Drugs for treating respiratory and nasal disorders are frequently administered in aerosol formulations through the mouth or nose.
  • One widely used method for dispensing such aerosol drug formulations involves making a suspension formula ⁇ tion of the drug as a finely divided powder in a liquefied gas known as a propellant.
  • the suspension is stored in a sealed container capable of withstanding the pres- sure required to maintain the propellant as a liquid.
  • the suspension is dispensed by activation of a dose metering valve affixed to the container.
  • a metering valve may be designed to consistently release a fixed, predeter ⁇ mined mass of the drug formulation upon each activation.
  • the propellant rapidly vaporizes, i.e., boils, leaving a fast moving cloud of very fine particles of the drug formulation.
  • This cloud is usually di ⁇ rected into the nose or mouth of the patient by a channeling device, e.g., a cylinder like or cone-like passage, with one of its ends attached to the outlet of the pressur ⁇ ized container, and the other end inserted in the mouth or nose of the patient.
  • the patient Concurrently with the activation of the aerosol dose metering valve, the patient in ⁇ hales the drug formulation particles into the lungs or nasal cavity.
  • Systems for dispensing drugs in this way are known as "metered dose inhalers" (MDI's). See Peter Byron, Respiratory Drug Delivery, CRC Press, Boca Raton, FL 1990 for a general background on this form of therapy.
  • One conventional method to test delivery of MDI's consists of taring each MDI and measuring the weight lost after the delivery of one dose. This method is accurate and adequate for testing a small number of samples. However, it is poorly suited for high speed production and packaging of MDI's.
  • a common method of testing drug delivery utilizes indirect pressure decay after activation of each MDI. This method does not render a direct mass meas- urement, but rather an approximation based upon the force exerted indirectly by the superheated vapor on a pressure transducer. As a consequence, this method is unable to detect MDI's which are marginally out of tolerance. Further, unac ⁇ ceptable inaccuracies result unless the production rate is less than about one and a half MDI's per second which is significantly below the optimal production rate, because at higher rates internal resonances tend to be induced. Therefore, multiple testing stations are used in the MDI production line leading to an increased maintenance burden and validation complications.
  • the present invention comprises a method for measuring the amount, i.e., mass, of a volatile liquid which comprises passing the mass over a heat loss measuring device, calculating the amount of heat loss accompanying the vapori ⁇ zation of the mass and correlating the heat loss to measurement of heat loss of known liquid aerosol mass made with the same device.
  • a particularly useful application of this method is the measurement of the mass of an aerosol propellant, delivered upon activation of a metering valve at ⁇ tached to a vessel containing an aerosol product.
  • This method is well suited as a quality assurance procedure in the production of metered dose inhalers (MDI's) because it can be used to measure delivery from a metering valve for each MDI with acceptable accuracy and precision without slowing production of the MDI's because the heat loss measurement can be taken very quickly.
  • the second aspect of the present invention is a method of quality assurance in the manufactur ⁇ ing of metered dose inhalers using the present method of measuring the mass of a liquid aerosol formulation.
  • Figure 1a depicts a perspective view of a testing apparatus for carrying out the method of the invention.
  • Figure 1b is an elevational cross section of the apparatus with a schematic diagram of the electrical connection for the generated signal.
  • Figures 2a, 2b and 2c are oscilloscope wave traces from testing mass ac ⁇ cording to the invention where the masses are within tolerable limits, too low and too high, respectively.
  • the liquid When a liquid is released from a sealed container, the liquid extracts heat from its environment, e.g., the surrounding air, to evaporate. The extraction of heat from the liquid's surrounding results in a lowering of the temperature of those surroundings.
  • a volatile liquid i.e., a liquid with a boiling point below or slightly above ambient temperature
  • the evaporation is very rapid and the consequential cooling of the air is observable even to the touch.
  • propellant 12 dichlorodifluoromethane
  • P12 1,1,1,2-tetrafluoroethane
  • 134a and "P134a,” has a boiling point of -26.5°C.
  • the valve of a propelled aerosol dispenser When the valve of a propelled aerosol dispenser is activated, the released propellant very rapidly evaporates to produce the aerosol, i.e., a fine suspension of the aerosol formulation in air and vaporized propellant. The rapid evaporation of the propellant extracts heat from the surrounding air producing a significant cooling effect.
  • the specific heat of the ambient air is relatively low compared to the latent heat of vaporization of the propellant and so a large drop in the temperature of the air occurs even if only a small amount of propellant is present
  • a mass of a volatile liquid to be meas ⁇ ured is discharged into a constant temperature and constant flow air stream and onto the probe of a heat loss measuring device placed downstream from the point of discharge.
  • the cooling effect of the vaporization of the liquid is sensed as a transient loss of heat from the area surrounding the probe and recorded as a tran ⁇ sient reduction of temperature of the air stream.
  • Two or more different, known masses of the same liquid are discharged under identical conditions and the cor- responding reduction in temperature recorded.
  • the mass of the sample is deter ⁇ mined by correlating the reduction in temperature resulting from its discharge with reduction in temperature caused by discharge of the samples of known mass.
  • the mass of the discharged volatile liquid is calculated as a function of the latent heat of vaporization of the liquid.
  • the volatile liquid is a propellant being used to disperse a drug formulation from an MDI
  • the amount of formulation discharged with each valve activation is di ⁇ rectly and consistently proportional to the mass of the propellant discharged. That is, knowledge of the mass of propellant discharged from an aerosol dispenser, an MDI, can be directly interpreted as knowledge of the amount of drug formulation dispensed. This knowledge is particularly important for quality assurance proce ⁇ dures in the manufacturing of MDI's and is discussed in detail hereinbeiow.
  • temperature and flow rate of the air stream be kept constant from measurement to measure ⁇ ment. Therefore, it is convenient to practice the present method within a partially enclosed chamber, i.e., a test chamber, wherein temperature and flow rate can be controlled and isolated from extraneous air currents, e.g., by means of enclosure within a tube having uniform cross section.
  • an apparatus 100 is provided to measure the mass of an aerosol.
  • a constant air flow 1 is maintained through the test chamber 2.
  • the dimensions of the test chamber are not critical, but must be sufficient to allow a constant air flow through the chamber while preventing extraneous air flow from the surroundings of the chamber.
  • the constant air flow may be generated by an air moving means such as a motorized fan 4 placed i) in close proximity to the exit of the test chamber as depicted in Figure 1a and 1b, ii) close proximity to the en- trance of the test chamber or iii) remotely located and connected by a duct to either the entrance or exit.
  • a baseline condition is established across sensing portion 6 of the probe of a heat loss measuring device 8, e.g., a hot film or hot wire anemometer, and is set as the reference condition, e.g., by a signal conditioner (SC) 10.
  • the SC 10 converts minute changes in the current required to maintain a predetermined temperature at the probe sensing portion 6 to an analog voltage (0-5 VDC). A decrease in temperature at the probe sensing portion 6 results in an increase in current required to maintain the wire or metallic film at the predetermined temperature.
  • the SC 10 also acts as a filter by averaging input signal to essentially eliminate electrical "noise” and provide a "clean,” linear signal.
  • a vessel 12 equipped with a metering dose valve 14 and containing a liquid aerosol propellant 16 is mounted in the test chamber 2 in an orientation whereby i) the discharge of propellant upon activation of the metering valve 14 is in the direc- tion of the air flow 1 and ii) the discharge 18 directly impinges on the sensing por ⁇ tion 6 of the probe of a heat loss measuring device 8 as shown in Figure 1b.
  • the discharge tube 20 which extends from the metering dose valve 14, is positioned by the vessel holder 22 in a fixed position against the opening in support ring 24 of the vessel holder 22.
  • the metering valve 14 may be activated by placing pressure against the end of the vessel 12 opposite from the metering valve 14.
  • pressure may be applied manually or mechanically, e.g. by r ⁇ ans of a plunger 26 connected to an electrical, pneumatic or other means to mova the plunger against the vessel 12.
  • the air with propellant can be passed through a water bath filter, for example, to remove powder from the gas.
  • the signal generated by the probe of the heat loss measuring device 8 is electronically and mathematically processed and compared to the cooling resulting from the discharges of the same liquid aerosol propellant under the same condi- tions by the waveform analyzer 28.
  • the processed signal is transmitted to a printer or recorder 30 where it is graphically recorded, and simultaneously trans- mitted to an oscilloscope 32 for rapid visualization.
  • the processed signal may also be further processed electronically and mathematically, e.g., by a program ⁇ mable logic controller, 34, to actuate devices which can reject from the production run those aerosol vessels with valves delivering drug formulation above or below the tolerated range.
  • the heat loss measuring device suitable for use in this invention should pref ⁇ erably: i) respond within 10 milliseconds to a temperature change, ii) be sensitive enough to sense changes of less than about .01 °C, iii) have an operational range from about 10°C to about 40°C with recovery to a baseline setting within 50 milli- seconds and iv) be capable of producing an electrical signal which can be ampli ⁇ fied, processed, recorded and viewed with conventional electronic components available to control and monitor manufacturing processes.
  • the speed of such a heat loss measuring device means that MDI's can be tested without a reduction in the optimal production rate of between 2 and 3 MDI's per second.
  • Anemometry employs a probe tipped by a heated, fine wire which is connected to a bridge circuit.
  • the bridge circuit is connected to an electronic amplifier which is connected to a device for visualizing the change of electrical signal, such as a recorder or oscilloscope.
  • a change in temperature of the hot wire alters its electrical resistance which unbalances the bridge circuit to generate an electrical signal proportional to the change of tem ⁇ perature of the wire.
  • the electrical signal may then be amplified, electronically and mathematically processed and presented in a useful, graphic form.
  • a very small, heated, insulated cylinder bearing a thin metallic film is used in lieu of the hot wire.
  • either a hot wire or hot film probe is acceptable and any reference hereinafter to either should be taken as including both.
  • the hot wire probe and the related circuitry is used to measure the flow of air or gases by measuring the cooling of the hot wire when it is placed in the flow. That is, the cooling effect is correlated to the rate of flow.
  • the hot wire anemometry system is essentially used as a sophisticated, electronic thermometer.
  • the theory and practice of hot wire/hot film anemometry is taught in Experimental Methods for Engineers, J. Holman and W. Gajda, Jr., ⁇ 7-7, McGraw-Hill, New York (1978). Further information, including specifications anemometry equipment offered for sale, is found in the brochure, "Hot Wire/Hot Film Anemometry Probes & Accessories," (1988) by TSI Incorporated, St. Paul, of Mfv
  • Aerosol vessels containing drug formulations such as MDI's may be sequen ⁇ tially subjected to the method of this invention by conventional mechanical means known in the art.
  • MDI's can be subjected to the method using conventional mechanical handling means as they come off the production line after filling at a rate of 2 or more per second.
  • conventional mechanical handling means as they come off the production line after filling at a rate of 2 or more per second.
  • the magnitude of temperature reduction and the duration of such reduction at the sensing part of the probe is directly proportional to the mass of the propel ⁇ lant discharged. Therefore, the electronic signal from the probe, processed by the signal conditioner and waveform analyzer and graphically displayed by the printer or recorder (or displayed on the oscilloscope) is also directly proportional to the mass of the propellant discharged.
  • Figures 2a, 2b and 2c depict graphs of the level of the electronic signal (voltage 201) in relation to duration (time 202) as would be displayed by the printer or recorder on the oscilloscope screen.
  • the area under the curve in each of the three graphs is directly proportional to the mass of the propellant discharged and, hence, the transient temperature reduction at the probe.
  • Figure 2a shows the pattern produced by discharge of propellant through a normal valve.
  • Figure 2b is a corresponding graph produced by a valve which discharges an unacceptably low amount of propellant while Figure 2c is produced by a valve which does not close properly after activation and, thus, discharges an excessive amount of propellant.
  • Two or more known masses of propellant can be sequentially discharged into a constant air flow onto the probe in the test chamber to establish a series of cor ⁇ responding standardized graphs.
  • An unknown mass of propellant may then be discharged and the area under the curve in the resulting graph is compared and correlated to the area under the curves produced by the discharges of the stan- dard masses.
  • the present method of measuring mass of aerosol propellant may be adapted as a method of quality assurance in the manufacture of MDI's which com ⁇ prise the following steps: a) determining the mass of the output of an MDI by the method described above,
  • step d Comparing the temperature reduction recorded in step c. with that produced under the same conditions by an essentially identical
  • MDI containing the same formulation but having a known mass of output upon activation, i.e., a "standardized MDI”.
  • the method of this invention may be adapted to test a wide variety of metered valve aerosol dispensers which use liquid propellants. It is particularly useful in the quality assurance of MDI's employed to deliver respiratory drugs. For exam ⁇ ple, this method may be used for quality assurance in the production of MDI's containing the respiratory drugs albuterol (sulbutamol), saimeterol, amiloride, fluticasone propionate and beclomethasone dipropionate.
  • Suitable liquids which can be measured by the present invention as aerosols include, but are not limited to, trichloromonofluoromethane, dichlorodifluoro ⁇ methane, 1,1,1,2-tetrafluoroethane, heptafluoropropane, tetrachlorofluoroethane, butane, isobutane and propane.
  • a standardized MDI containing a suspension of albuterol in P12 is placed into an apparatus essentially as depicted in Figures 1a and 1b with the tip of the dis ⁇ charge tube about 30 mm from the sensing portion of a TSI model 1210-T1.5 hot wire anemometer probe supplied by TSI Incorporated.
  • a constant air flow of about 20 cfm to about 30 cfm is maintained through the test chamber by a tubeaxial fan supplied by Radio Shack.
  • the signal from the anemometer is transmitted by coaxial, shielded cable (CSC) to a model 157 internally installed signal conditioner supplied by TSI, Inc.
  • CSC coaxial, shielded cable
  • the conditioned signal is then transmitted by CSC to a model 170 Gould waveform analyzer supplied by General Electric Instruments, inc.
  • the waveform analyzer transmits a signal by CSC to a chart recorder or a high speed printer and simulta ⁇ neously by CSC to a model 4073 Gould digital storage oscilloscope supplied by General Electric Instruments, Inc.
  • the signal from the waveform analyzer is also transmitted to an Allen-Bradley, Family 5, programmable logic controller. With the constant air flow through the test chamber the signal from the anemometer is set as the baseline condition.
  • a standard MDI the output of which has been previously measured by taring and measuring the weight lost after a discharge, is activated by a downward thrust of the plunger.
  • the resulting temperature drop sensed by the anemometer is re ⁇ corded electronically in the signal conditioner as the standard.
  • the out- puts of two or more standardized MDI's are recorded and electronically and mathe ⁇ matically averaged in the signal conditioner to set the standard.
  • the outputs of two or more MDI's may be correlated with the corresponding drop in temperature upon discharge.
  • Such correlation may conveniently be done electronically and mathe ⁇ matically in the signal conditioner to yield a standard curve relating mass of output to resulting temperature drop.
  • the mass of the output of an MDI being tested can be determined by relating the temperature drop resulting from its discharge to the corresponding output mass on the standard curve.
  • the standardized MDI is removed and MDI's from the production run to be tested are sequentially placed in the test chamber and activated in the same way as was the standardized MDI.
  • the signal generated by the anemometer as a re- suit of the temperature reduction about the probe upon discharge of each MDI is electronically and mathematically compared with the signal previously generated by one or more standardized MDI's. If the signal generated by discharge of a sample MDI is outside the preset tolerance, a signal is transmitted to the Allen- Bradley programmable logic controller which, in turn, activates a means to remove the out-of-tolerance MDI from the production run.
  • the output of an MDI being tested can be observed within 300 miliseconds on the oscilloscope. This rapid, visual indication of the outputs of the production run MDI's is useful to the production line operator in spotting defect trends and detect ⁇ ing substandard lot of MDI valves. A permanent record can be made with the re- corder or printer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Fluid Mechanics (AREA)
  • General Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pulmonology (AREA)
  • Anesthesiology (AREA)
  • Biophysics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Investigating Or Analyzing Materials Using Thermal Means (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

La présente invention se rapporte à un procédé destiné à mesurer la quantité, c'est-à-dire la masse, d'un liquide volatil, et qui consiste à faire passer la masse (18) sur un dispositif de mesure de perte de chaleur (6, 8), à calculer la quantité de perte de chaleur due à la vaporisation de la masse, et à mettre en corrélation la perte de chaleur avec la quantité de perte de chaleur de la masse aérosol liquide connue obtenue avec le même dispositif. Le procédé est notamment utile pour garantir des doses uniformes aux différents récipients aérosols (12).
PCT/US1993/003620 1992-04-21 1993-04-19 Procede de test des aerosols Ceased WO1993020956A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP51864193A JP3249121B2 (ja) 1992-04-21 1993-04-19 噴霧検査方法
EP93912291A EP0637270B1 (fr) 1992-04-21 1993-04-19 Procede de mesure d'une quantite d'aerosol
DE69332201T DE69332201T2 (de) 1992-04-21 1993-04-19 Aerosolmassenmessverfahren
FI944910A FI944910L (fi) 1992-04-21 1993-04-19 Aerosolin testausmenetelmä
AT93912291T ATE222353T1 (de) 1992-04-21 1993-04-19 Aerosolmassenmessverfahren
AU42894/93A AU668183B2 (en) 1992-04-21 1993-04-19 Aerosol testing method

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US07/871,873 US5261538A (en) 1992-04-21 1992-04-21 Aerosol testing method
US07/871,873 1992-04-21

Publications (1)

Publication Number Publication Date
WO1993020956A1 true WO1993020956A1 (fr) 1993-10-28

Family

ID=25358349

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1993/003620 Ceased WO1993020956A1 (fr) 1992-04-21 1993-04-19 Procede de test des aerosols

Country Status (9)

Country Link
US (1) US5261538A (fr)
EP (1) EP0637270B1 (fr)
JP (1) JP3249121B2 (fr)
AT (1) ATE222353T1 (fr)
AU (1) AU668183B2 (fr)
CA (1) CA2134085A1 (fr)
DE (1) DE69332201T2 (fr)
FI (1) FI944910L (fr)
WO (1) WO1993020956A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011089490A1 (fr) * 2010-01-20 2011-07-28 Koninklijke Philips Electronics N.V. Capteur de flux et dispositif de distribution d'aérosol
EP2604995A1 (fr) * 2011-12-16 2013-06-19 Deva Holding Anonim Sirketi Extracteur de contenu pour un inhalateur doseur

Families Citing this family (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USD357261S (en) 1993-12-30 1995-04-11 Morgan Clinton D Florescent bulb disposal
DE4432714C1 (de) * 1994-09-14 1995-11-02 Deutsche Forsch Luft Raumfahrt Verfahren zur Größenbestimmung luftgetragener Wassertropfen
TR199701168T1 (xx) 1995-04-14 1998-05-21 Glaxo Wellcome Inc. Flutikazon Propionat i�in �l��lm�� doz inhaleri.
BR9604977A (pt) 1995-04-14 1998-06-09 Glaxo Wellcome Inc Inalador de dose medida sistema inalador de dose medida e uso do mesmo
EE03997B1 (et) * 1995-04-14 2003-04-15 Glaxo Wellcome Inc. Albuterooli doseeriv inhalaator
EA000889B1 (ru) * 1995-04-14 2000-06-26 Глаксо Веллкам Инк. Дозирующий ингалятор дипропионата беклометазона
US5753801A (en) * 1996-08-02 1998-05-19 Thiele Engineering Company Canister tester
AU7288198A (en) * 1997-04-30 1998-11-24 Thomas M. Kuhl Medical inhaler with thermochromic gauge
GB9814717D0 (en) * 1998-02-23 1998-09-02 Bespak Plc Improvements in drug delivery devices
US20030209453A1 (en) * 2001-06-22 2003-11-13 Herman Craig Steven Method and package for storing a pressurized container containing a drug
US6315112B1 (en) * 1998-12-18 2001-11-13 Smithkline Beecham Corporation Method and package for storing a pressurized container containing a drug
US6352152B1 (en) 1998-12-18 2002-03-05 Smithkline Beecham Corporation Method and package for storing a pressurized container containing a drug
US6393900B1 (en) 1999-11-17 2002-05-28 Smithkline Beecham Corporation Aerosol can content analyzer workstation
US20040089561A1 (en) * 1999-11-23 2004-05-13 Herman Craig Steven Method and package for storing a pressurized container containing a drug
EP1259429A2 (fr) 2000-03-01 2002-11-27 Glaxo Group Limited Inhalateur-doseur
AU2001270074A1 (en) 2000-06-22 2002-01-02 Glaxo Group Limited Method and package for storing a pressurized container containing a drug
GB0016123D0 (en) * 2000-07-01 2000-08-23 Glaxo Group Ltd Valve for aerosol container
WO2002024552A2 (fr) 2000-09-18 2002-03-28 Glaxo Group Limited Recipient d'aerosol doseur recouvert deux fois ou plus de polymeres de fluorocarbure
GB0025092D0 (en) * 2000-10-13 2000-11-29 Glaxo Group Ltd Medicament dispenser
GB0031176D0 (en) 2000-12-21 2001-01-31 Glaxo Group Ltd Medicament dispenser
WO2002103318A1 (fr) * 2001-06-15 2002-12-27 Smithkline Beecham Corporation Appareil et procede de mesure des forces exercees sur des ensembles valve de recipients de distribution de doses mesurees pendant la fabrication de ces ensembles
GB0122725D0 (en) 2001-09-21 2001-11-14 Glaxo Group Ltd Drug dispensing components
GB0125380D0 (en) * 2001-10-23 2001-12-12 Glaxo Group Ltd Medicament dispenser
AU2003272527A1 (en) * 2002-09-19 2004-04-08 Glaxo Group Limited System and method to stress test aerosol inhalation devices
US7624731B2 (en) * 2005-03-16 2009-12-01 Dennis R Walstrom HME/MDI apparatus having MDI in parallel to HME
AU2010324997A1 (en) 2009-11-24 2012-05-31 Gilead Sciences, Inc. Inhaled fosfomycin/tobramycin for the treatment of chronic obstructive pulmonary disease
WO2011081937A1 (fr) 2009-12-15 2011-07-07 Gilead Sciences, Inc. Composés de type corticostéroïde-bêta-agoniste-antagoniste muscarinique pour applications thérapeutiques
JP2013517082A (ja) * 2010-01-20 2013-05-16 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ 温度に基づくエアロゾル検出
US8367829B2 (en) 2010-05-10 2013-02-05 Gilead Sciences, Inc. Bi-functional pyrazolopyridine compounds
AU2011253203A1 (en) 2010-05-10 2012-11-22 Gilead Sciences, Inc. Bifunctional quinoline derivatives
SG10201505022WA (en) 2010-06-24 2015-07-30 Gilead Sciences Inc Pyrazolo [1, 5 -a] pyrimidines as antiviral agents
SI2595980T1 (sl) 2010-07-22 2014-11-28 Gilead Sciences, Inc. Postopki in sestavki za zdravljenje paramyxoviridae virusnih infekcij
TW201305185A (zh) 2010-09-13 2013-02-01 Gilead Sciences Inc 用於抗病毒治療之２’－氟取代之碳－核苷類似物
AR086745A1 (es) 2011-06-27 2014-01-22 Parion Sciences Inc 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida
EP3932931B1 (fr) 2012-03-13 2024-11-20 Gilead Sciences, Inc. Nébuliseur comprenant une composition pharmaceutique comprenant analogues de carba-nucléoside 2'-substitués pour traitement antiviral
LT2838900T (lt) 2012-04-17 2019-11-11 Gilead Sciences Inc Junginiai ir būdai, skirti priešvirusinei terapijai
EA201990616A3 (ru) 2012-05-29 2019-12-30 Парион Сайэнс, Инк. Дендримероподобные аминоамиды, обладающие активностью блокаторов натриевых каналов, для лечения сухости глаз и других заболеваний слизистых оболочек
JP6392242B2 (ja) 2012-12-17 2018-09-19 パリオン・サイエンシィズ・インコーポレーテッド 粘膜への水分付与が不十分であることが好都合である疾患の治療に有用なクロロ−ピラジンカルボキサミド誘導体
ES2674665T3 (es) 2012-12-17 2018-07-03 Parion Sciences, Inc. Compuestos de 3,5-diamino-6-cloro-N-(N-(4-fenilbutilo)carbamimidoilo)-pirazina-2-carboxamida
NZ709197A (en) 2012-12-17 2020-06-26 Parion Sciences Inc 3,5-diamino-6-chloro-n-(n-(4-phenylbutyl)carbamimidoyl) pyrazine-2- carboxamide compounds
UA119050C2 (uk) 2013-11-11 2019-04-25 Ґілеад Саєнсиз, Інк. ПІРОЛО[1.2-f][1.2.4]ТРИАЗИНИ, ЯКІ ВИКОРИСТОВУЮТЬСЯ ДЛЯ ЛІКУВАННЯ РЕСПІРАТОРНО-СИНЦИТІАЛЬНИХ ВІРУСНИХ ІНФЕКЦІЙ
TWI678369B (zh) 2014-07-28 2019-12-01 美商基利科學股份有限公司 用於治療呼吸道合胞病毒感染之噻吩並［３,２-ｄ］嘧啶、呋喃並［３,２-ｄ］嘧啶及吡咯並［３,２-ｄ］嘧啶化合物類
TWI673283B (zh) 2014-08-21 2019-10-01 美商基利科學股份有限公司 ２’－氯胺基嘧啶酮及嘧啶二酮核苷類
US10330638B2 (en) 2017-01-16 2019-06-25 Wyatt Technology Corporation Method and apparatus to characterize pressurized liquid sample
ES3001984T3 (en) 2019-12-24 2025-03-06 Carna Biosciences Inc Diacylglycerol kinase modulating compounds
CA3171648A1 (fr) 2020-02-18 2021-08-26 Gilead Sciences, Inc. Composes antiviraux
TWI791193B (zh) 2020-02-18 2023-02-01 美商基利科學股份有限公司 抗病毒化合物
TWI883391B (zh) 2020-02-18 2025-05-11 美商基利科學股份有限公司 抗病毒化合物
TWI874791B (zh) 2020-02-18 2025-03-01 美商基利科學股份有限公司 抗病毒化合物
CA3181922A1 (fr) 2020-05-01 2021-11-04 Gilead Sciences, Inc. Composes de 2,4-dioxopyrimidine inhibant cd73
AU2022297367B2 (en) 2021-06-23 2025-04-10 Gilead Sciences, Inc. Diacylglyercol kinase modulating compounds
JP7651018B2 (ja) 2021-06-23 2025-03-25 ギリアード サイエンシーズ， インコーポレイテッド ジアシルグリセロールキナーゼ調節化合物
JP7654118B2 (ja) 2021-06-23 2025-03-31 ギリアード サイエンシーズ， インコーポレイテッド ジアシルグリセロールキナーゼ調節化合物
WO2022271677A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés de modulation de la diacylglycérol kinase
EP4422756A1 (fr) 2021-10-29 2024-09-04 Gilead Sciences, Inc. Composés cd73

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU911232A1 (ru) * 1980-06-26 1982-03-07 Институт Экспериментальной Метеорологии Способ дистанционного измерени средних размеров частиц аэрозол
SU1029083A1 (ru) * 1980-09-30 1983-07-15 Уфимский авиационный институт им.Орджоникидзе Термоанемометрический преобразователь
SU1191803A1 (ru) * 1983-05-17 1985-11-15 Организация П/Я В-8413 Измеритель молекул рной массы
SU1314270A1 (ru) * 1985-03-20 1987-05-30 Среднеазиатский Филиал Государственного Всесоюзного Научно-Исследовательского Технологического Института Ремонта И Эксплуатации Машинно-Тракторного Парка Термоанемометр
JPS6429150A (en) * 1987-07-24 1989-01-31 Nec Corp Voice reply system for private branch of exchange
JPH03220447A (ja) * 1990-01-26 1991-09-27 Nec Corp Ｔｇ―ｇｃ／ｍｓ装置

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE408828C (de) * 1924-08-19 1925-01-27 Bbc Brown Boveri & Cie Dampfmesser mit selbsttaetiger Temperaturkorrektur
DE590825C (de) * 1930-01-29 1934-01-12 Siemens & Halske Akt Ges Kalorischer Dampfmengen- oder Waermemengenmesser
DE814052C (de) * 1949-04-24 1951-09-20 Heinz Dr Gruess Kalorimetrischer Dampfmengenmesser
DE2602867A1 (de) * 1976-01-27 1977-07-28 Wolfgang Niehaus Verfahren und vorrichtung zum automatischen dosieren von fluessigkeitsmengen
GB2033582B (en) * 1978-10-31 1983-05-11 Dart Ausschank Rat Tech Liquid metering method and device
JPH0322047A (ja) * 1989-06-20 1991-01-30 Nec Corp ファイルの機密保護方式

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU911232A1 (ru) * 1980-06-26 1982-03-07 Институт Экспериментальной Метеорологии Способ дистанционного измерени средних размеров частиц аэрозол
SU1029083A1 (ru) * 1980-09-30 1983-07-15 Уфимский авиационный институт им.Орджоникидзе Термоанемометрический преобразователь
SU1191803A1 (ru) * 1983-05-17 1985-11-15 Организация П/Я В-8413 Измеритель молекул рной массы
SU1314270A1 (ru) * 1985-03-20 1987-05-30 Среднеазиатский Филиал Государственного Всесоюзного Научно-Исследовательского Технологического Института Ремонта И Эксплуатации Машинно-Тракторного Парка Термоанемометр
JPS6429150A (en) * 1987-07-24 1989-01-31 Nec Corp Voice reply system for private branch of exchange
JPH03220447A (ja) * 1990-01-26 1991-09-27 Nec Corp Ｔｇ―ｇｃ／ｍｓ装置

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Hot wire/Hot Film Anemometry Probes and Accessories", TSI Inc., St. Paul, Mn., 1988. *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011089490A1 (fr) * 2010-01-20 2011-07-28 Koninklijke Philips Electronics N.V. Capteur de flux et dispositif de distribution d'aérosol
CN102762246A (zh) * 2010-01-20 2012-10-31 皇家飞利浦电子股份有限公司 流传感器以及气雾剂递送装置
EP2604995A1 (fr) * 2011-12-16 2013-06-19 Deva Holding Anonim Sirketi Extracteur de contenu pour un inhalateur doseur
WO2013087853A1 (fr) * 2011-12-16 2013-06-20 Deva Holding Anonim Sirketi Extracteur de contenu pour inhalateurs-doseurs

Also Published As

Publication number Publication date
AU668183B2 (en) 1996-04-26
DE69332201D1 (de) 2002-09-19
DE69332201T2 (de) 2003-05-28
ATE222353T1 (de) 2002-08-15
FI944910A7 (fi) 1994-10-19
EP0637270A1 (fr) 1995-02-08
JP3249121B2 (ja) 2002-01-21
JP2000515238A (ja) 2000-11-14
US5261538A (en) 1993-11-16
EP0637270A4 (fr) 1997-05-28
EP0637270B1 (fr) 2002-08-14
AU4289493A (en) 1993-11-18
FI944910A0 (fi) 1994-10-19
CA2134085A1 (fr) 1993-10-28
FI944910L (fi) 1994-10-19

Similar Documents

Publication Publication Date Title
US5261538A (en) Aerosol testing method
CN102711881B (zh) 具有基于温度的气雾剂检测器的气雾剂递送系统
US20120285236A1 (en) Method of using a temperature-based aerosol detector
US20120291779A1 (en) Flow sensor and aerosol delivery device
EP1107810B1 (fr) Distributeur
Kamin et al. Mass output and particle size distribution of glucocorticosteroids emitted from different inhalation devices depending on various inspiratory parameters
WO1992007599A1 (fr) Dispositif inhalateur
US20050016527A1 (en) Method and apparatus for testing a metered dose inhaler unit
Visscher Standard psychrometers: a matter of (p) references
Martin et al. Investigating the evaporation of metered-dose inhaler formulations in humid air: single droplet experiments
US7659725B2 (en) Method for assessing the suitability of metered dose inhaler actuators
Halbert et al. Inhalation simulation and the effects of lung environmental conditions on consumer aerosol products and NaCl aerosol
Willbanks Recovery characteristics of a single-shielded self-aspirating thermocouple probe at low pressure levels and subsonic speeds
Geerse et al. Electrospray as means to produce monodisperse drug particles
Haak et al. Wind tunnel calibration of the''Arcasonde 1-A''at simulated altitudes between 35 and 57 km
Uddin QUALITY CONTROL TESTS FOR PHARMA-CEUTICAL AEROSOLS
Furtado et al. Frost/Dew Point Temperature and Relative Humidity Measurements: Primary and Secondary Calibration Methods
Reehorst et al. Results and Conclusions From the NASA Isokinetic Total Water Content Probe 2009 IRT Test
MCLAIN DEVELOPMENT OF A HIGH VELOCITY SPRAY DRYER
WO2009054795A1 (fr) Dispositif pour mesurer l'alignement de la valve d'une cartouche d'inhalateur-doseur pressurisée
Severin Comparative Meteorological Testing of the AMT-13 Dropsonde and JOOX-series Rawinsonde in an Environmental Wind Tunnel
Mitchell Jolyon Mitchell Inhaler Consulting Services, Inc.
HK1193363A (en) Apparatus, system and method for measuring resistance of an inhaler

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR CA CH CZ DE DK ES FI GB HU JP KP KR KZ LK LU MG MN MW NL NO NZ PL PT RO RU SD SE SK UA US VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 1993912291

Country of ref document: EP

Ref document number: 944910

Country of ref document: FI

ENP Entry into the national phase

Ref document number: 1993 518641

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2134085

Country of ref document: CA

WWP Wipo information: published in national office

Ref document number: 1993912291

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWG Wipo information: grant in national office

Ref document number: 1993912291

Country of ref document: EP